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New botox super-toxin has its details censored

By Debora MacKenzie

A new type of botulinum toxin – the deadliest substance known – has been discovered. Because it does not yet have an antidote, the DNA sequence behind it has been withheld from public databases. This is the first time a sequence has been kept secret over security concerns.

Injecting a mere 2 billionths of a gram, or inhaling 13 billionths of a gram, of the protein botulinum produced by the soil bacterium Clostridium botulinum will kill an adult. The toxin blocks the release of acetylcholine, the chemical secreted by nerves that makes muscles work. People who accidentally ingest it, as can happen when the bacteria grow in food, develop botulism and often die of paralysis.

Victims are treated with monoclonal antibodies, which are immune proteins produced artificially that react with the seven families of botulinum – named A to G – discovered so far.

Stephen Arnon and colleagues at the California Department of Public Health in Sacramento report this week that they have found an 8th toxin – type H – in the faeces of a child who had the typical symptoms of botulism.

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Secret sequence

The team sequenced the bacterial DNA that codes for the toxin, and found it constitutes a separate branch on the botulinum family tree.

The new toxin only reacted weakly with a few of the standard antibodies supplied by the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. None of these antibodies protected mice from the effects of the toxin.

The team also tried to grow antibodies to the type H toxin in rabbits. While these did protect mice, a larger dose was required than is needed to treat families A to G. Further work to develop a stronger antibody, scale up production and test it for safety in humans will be needed before there is an effective remedy for toxin H.

Normally the gene sequence of the bacteria that create the toxin would be released to the public database GenBank, but it was decided that this was too risky at present.

Toxic debate

Editors of the Journal of Infectious Diseases, where the research was published, write&colon; “Because no antitoxins as yet have been developed to counteract the novel C. Botulinum toxin, the authors had detailed consultations with representatives from numerous appropriate US government agencies.”

This included the US Army’s infectious diseases laboratory, the US Department of Homeland Security, the Centers for Disease Control and Prevention and various other government health departments.

The agencies approved the papers published this week, but without the gene sequence for the toxin. This will be published once an effective treatment is available.

Dual use research

Publishing the sequence would have posed “an immediate and unusually serious risk to society”, said David Relman, at Stanford University in an accompanying comment. Relman was one of six members of a US government committee last year who disagreed with a decision to publish research showing how to make deadly H5N1 bird flu readily transmissible among mammals.

That research was christened “dual use research of concern”, because it carries the possibility of use for nefarious as well as scientific and medical ends.

The idea of a bioterrorist putting botulinum in food – dropping a few grams into a milk truck for example – is a longstanding nightmare of biosecurity experts.

Arnon’s team warns that there are probably other botulinum toxins in nature, waiting to be discovered.